1. Field of the Invention
This invention relates to dermatologic agents which reduce irritation caused by the topical application of an active ingredient used to treat a skin condition. More particularly, ascorbic acid or a derivative product is added to a cosmetically and/or pharmaceutically acceptable vehicle to reduce the irritation reaction.
2. State of the Art
Human skin is a complex organ which extends over the entire body. There are different types of skin at different locations on the body. For example, facial skin differs from skin on the scalp; and skin on the front (palm) of the hand is different from that on the back. Although the type of skin can vary over a person's body, skin is generally composed of two main layers of tissue. The outermost layer is the epidermis or cuticle. It is composed of three superficial and two deep layers. The derma, corium, or cutis vera, the true skin, is composed of a papillary layer above and a reticular layer below.
Since ancient times, a variety of substances have been used to improve skin appearance. Early techniques were generally directed to the outermost layer of skin, or to ailments found on the true skin. More recently, efforts have been made to rejuvenate the skin and reclaim elasticity or suppleness lost from aging and/or exposure to sunlight (UV radiation) and weather.
U.S. Pat. No. 3,897,537 describes several .alpha.-hydroxy acids, keto acids and esters thereof which are useful in the treatment of ichthyosiform dermatoses. These conditions are characterized by a fish-scale appearance typically caused by hereditary disorders. This patent contemplates daily application of a composition with at least one lower organic hydroxy acid, keto acid or esters thereof in the range from 1 to 20 weight percent.
Alpha-hydroxy acids and keto acids have also been recognized as useful for treating a number of other skin conditions. For instance, U.S. Pat. No. 3,920,835 describes a treatment for skin lesions which accompany disturbed keratinization. Examples of this condition include dandruff, acne, palmar and plantar (hand and foot) hyperkeratosis and palmar and plantar callouses which are secondary manifestations of eczema or chronic friction. For additional disclosures, please see U.S. Pat. Nos. 3,984,566 and 3,988,470.
Acne (acne vulgaris) is a very common condition for which a variety of prescription and over-the-counter remedies are available. Benzoyl peroxide is a common over-the-counter remedy. But, the active ingredient is a strong oxidizing agent which may cause allergic or dermatitic reactions. U.S. Pat. No. 4,021,572 describes the use of lactamides and quaternary ammonium lactates for acne treatment. Lactic acid is a useful, but potentially irritating compound. Non-irritating compositions are formed when lactic acid is first reacted with a suitable base, such as ammonium hydroxide or an alkyl amine.
The condition of dry skin is characterized by cracking, flaking and/or scaling. U.S. Pat. No. 4,105,733 describes the treatment of this condition with free acids, or the amide and/or ammonium salts of selected acids, including .alpha.-hydroxy and keto acids.
U.S. Pat. Nos. 4,363,815; 4,380,549 and 5,091,171 should also be noted for their various disclosures of .alpha.-hydroxy and/or keto acids and various derivatives for the treatment of multiple ailments. Exemplary derivatives of these compounds include the peroxide, amide, lactone, anhydride, ester and polymeric forms, as well as various organic or inorganic salts. Known acids and/or their derivatives may be combined with amphoteric compounds (such as peptides and polypeptides) or pseudoamphoteric compounds (such as creatinine). In addition to the skin conditions already mentioned, these compositions are useful for treating psoriasis, pruritus, age spots, melasmas, wrinkles, warts, blemishes, hyperpigmentation, inflammatory dermatoses and the like.
Compositions which reduce dryness or flakiness and improve the suppleness or smoothness of skin are also known in the art. These compositions comprise effective amounts of an hydroxylated carboxylic acid having 4-12 carbon atoms, in combination with a cosmetically acceptable vehicle other than water--which is not excluded, but another vehicle must be present.
Additional acne medications are available for use over-the-counter. These formulations typically contain sulfur, resorcinol, salicylic acid and benzoyl peroxide or combinations thereof. Recent products include retinol (Vitamin A) and various derivatives, such as retinoic acid, also known as tretinoin and Retin-A, have been used for the treatment of severe acne. See, for example, U.S. Pat. No. 3,006,939 which relates to retinoic acid; and U.S. Pat. No. 4,826,828 which describes the preparation of stable retinol compositions, especially for reducing wrinkles.
U.S. Pat. Nos. 3,932,665 and 4,934,114 disclose the use of retinal (Vitamin A aldehyde) for the treatment of ache and skin keratoses, respectively. U.S. Pat. No. 3,060,229 also illustrates the state of this art. Retinal and it derivatives have found application in the treatment of wrinkles, warts, psoriasis, eczema, dandruff and like conditions (EP-A2-0 391 033). There are also suggestions that tretinoin can heal or reverse the effects of photoaging. Representative publications include Kligman, "Current Status of Topical Tretinoin in the Treatment of Photoaged Skin," Drugs & Aging, 2(1):7-13 (1992); Ellis, "Tretinoin: Its Use in Repair of Photodamage," and Zelickson, "Topical Tretinoin in Photoaging: An Ultrastructural Study," both presented in the Journal of Cutaneous Aging & Cosmetic Dermatology, Vol. 1, No. 1, pp. 33-40 and 41-47 (1988).
Vitamin C (ascorbic acid) and its derivatives are other compounds which have been topically applied as the active ingredient for the treatment of various skin conditions. U.S. Pat. No. 4,983,382 describes the preparation of stabilized ascorbic acid compositions for topical application. See also, U.S. Pat. Nos. 5,140,043 and 5,122,536 which describe the use of ascorbic acid for preventing ultraviolet damage and treating psoriasis.
With these and other known ingredients, end-users may suffer from irritation or dermatitis due to the active ingredient, the vehicle or a combination of both. The source of these dermatoses is not always the same, and the reason is not always apparent. For example, a skin rash may result because the active ingredient or vehicle causes a dry condition similar to the action of soap. Irritation may also arise from the transdermal administration of an active ingredient. And, the conformational and/or stereochemistry of the active ingredient may induce an allergic-type irritation.
It will be appreciated that any irritation caused by treatment for a given skin condition is undesirable. These conditions typically have a non-aesthetic appearance, which is often the reason a patient seeks treatment in the first instance. Poor aesthetic appearance of the skin may be (or may appear to be) aggravated by treatment when irritation is caused by the active ingredient. Adverse cosmetic reactions may worsen with continuing use of a particular active ingredient over an extended period of time. These negative results can be quite disturbing to the patient. And, they may prompt a patient to discontinue treatment or neglect the original condition. The end-user or physician may reduce the number of treatments or lower the concentration of active ingredient (again reducing the effectiveness of treatment).
Therefore, it would be desirable to reduce or eliminate irritation resulting from the treatment of skin conditions, regardless of whether this condition is caused by the active ingredient, the vehicle or some combination thereof.
It may also be desirable to topically apply higher concentrations of active ingredient for better efficacy or to enhance the effect of a pre-selected active ingredient, thereby permitting less frequent or less concentrated administration of the active ingredient.